作者：危智盛，王晓辉，洪铭范，苏全喜，余青云，臧林泉，潘雪刁
【摘要】 目的 研究不同剂量甲泼尼龙(MP)作用于实验性变态反应性脑脊髓炎(EAE)大鼠模型后，剪接因子SRp30c的表达及其与疗效的关系，探讨MP治疗作用及发生激素抵抗的可能机制。方法 构建Wistar大鼠EAE模型，将EAE大鼠分成大剂量组、小剂量组、模型对照组，分别通过尾静脉注射MP 100 mg/kg、25 mg/kg、等容量生理盐水;另取未造模大鼠作为正常对照组，予等容量生理盐水注射。给药5d后处死大鼠，提取新鲜脊髓组织行RTPCR，检测SRp30c mRNA表达，分析其与疗效的关系。结果 SRp30c在各组均有表达，大、小剂量组SRp30c mRNA表达明显高于模型组、正常对照组，差异有显著性;不同大鼠Kono评分改善的差值与其SRp30c mRNA表达值呈负相关(r=-0.583，P<0.05)。结论 SRp30c表达与病情及MP剂量无直接关系，但与疗效呈负相关，表明其与糖皮质激素敏感性下降有着密切的关系，EAE模型发生激素抵抗的机制中SRp30c扮演着重要的角色。
【关键词】 甲泼尼龙 实验性变态反应性脑脊髓炎 糖皮质激素抵抗 SRp30c
Abstract:Objective To investigate the expression of alternative splicing factor SRp30c and the therapeutic effect of methylprednisolone (MP) and the correlation between SRp30c and the therapeutic effect in experimental allergic encephalomyelitis (EAE) in rats after treatment with MP at different doses,and to explore the possible mechanisms of glucocorticoid resistance. Methods Established EAE model with Wistar rats and the animal model were divided into three groups (highdose group,lowdose group,and model control group). Highdose group and lowdose group were treated by intravenous injection MP through caudal vein at the doses of 100 mg/kg and 25 mg/kg respectively. Model control group and another normal control group were administered with normal saline at the same volume. The rats were executed after 5day therapy,then the spinal cord was extracted and used to detect the expression of SRp30c mRNA by reverse transcription polymerase chain reaction. The relationship between SRp30c and the therapeutic effect was studied. Results SRp30c was expressed in every group. The expression level of highdose group and lowdose group were significant higher than that of model and normal control group. There was linear correlation between the expression of SRp30c mRNA and the GN score changes (r=-0.583，P<0.05). Conclusion There was neither direct correlation between the expression of SRp30c and pathogenesis,nor the dose of MP. While it had a negative correlation between SRp30c and therapeutic effect. Therefore,it suggested that SRp30c contributed to the declining sensitivity of glucocorticoid,and it might play an important role in the mechanisms of glucocorticoid resistance in EAE.
Key words:methylprednisolone;experimental allergic encephalomyelitis;glucocorticoid resistant;SRp30c
多发性硬化(multiple sclerosis，MS)是一种常见的中枢神经系统白质脱髓鞘病变，临床对于MS急性发作和复发常首选甲泼尼龙(methylprednisolone，MP)冲击治疗。然而，MP使用的剂量一直存在争议，现常用的有500，1 000，2 000 mg/d。超大剂量能否提高疗效及有无诱导糖皮质激素(glucocorticoid，GC)抵抗，引起临床关注。糖皮质激素抵抗(glucocorticoid resistant)发生机制非常复杂，其中剪接因子家族中SRp30c与激素抵抗密切相关[1，2]。本研究通过对实验性变态反应性脑脊髓炎(experimental allergic encephalomyelitis，EAE)大鼠模型MP治疗后神经组织中SRp30c mRNA表达情况进行分析，探讨MP治疗作用及MS发生激素抵抗的可能机制。
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